tbuckley/cabot-search huggingface dataset:
A health economic model to assess the impact of prehabilitation on hospital cost savings in gastrointestinal cancer, modelled on English National Health Service tariff.
Authors: Bernarda Zamora Zamora Talaya, Krishna Moorthy, Katerina Savva, Melody Ni
Journal: Journal of Clinical Oncology (2023)

6648 Background: Prehabilitation is increasingly being recognised as a high-priority intervention to improve physical and psychological health in cancer patients, prevent treatment-related functional decline and to reduce the incidence and severity of post-surgical complications. The aim of this study is to develop a health economic (HE) model to evaluate the impact of prehabilitation in patients undergoing gastrointestinal cancer surgery. Methods: The objective of the HE model is to estimate the impact of prehabilitation on reducing treatment costs. Data was extracted from systematic reviews and meta-analysis on the effects of prehabilitation in gastrointestinal cancer surgery to identify: i) treatment pathway, ii) prehabilitation components (nutrition/exercise/psychological intervention), and iii) effects on three study outcomes (length of hospital stay, reduction of post-operative complications, and reduced Intensive Care Unit (ICU) stay). The modelling study accounts for the number of hospital admissions and unit costs from NHS hospitals, including cost per bed-day from NHS Reference costs 2017-18 and complication costs and ICU cost from NHS Reference National Cost Schedule 2019-20. Double counting has been corrected to account for the compounded effects on length of stay and complications. The HE model considers the average effect of each study outcome and their confidence intervals. This provides a range of potential impact of prehabilitation in terms of cost reduction based on NHS tariff. Results: Patient weighted average cost savings from prehabilitation was £785, excluding ICU costs. Breakdown of cost savings include £178.6 from reduced length of hospital stay, £214.8 and £434.5 cost savings originating from reductions in minor and major complications, respectively (excluding ICU complication costs). ICU cost savings from prehabilitation were £1,620. For the NHS, based on 237,000 annual surgical procedures, this amounts up to £186,082,321 in cost savings, from a reduction in complications and 421,840 hospital days, and £52,761,227 from ICU stay. Conclusions: In addition to the impact on post-operative complications and hospital stay, this study has demonstrated that prehabilitation results in significant costs savings to healthcare systems. The cost savings are largely from a reduction in the incidence and severity of post-operative complications. The latter contributing to reduced ICU costs.
Prognostic value of total tumor volume with 68Ga DOTATOC PET/CT in predicting response to 177-Lu-DOTATOC treatment in metastatic well-differentiated neuroendocrine tumors (NETs).
Authors: Elizabeth Vega-Zolano, Erika Ruiz, German Caderillo-Ruiz, Consuelo Diaz, Marytere Herrera, Liliana Patricia Torres Agredo, Irma Soldevilla-Gallardo, Emiliano Michel-Sanchez, Francisco Osvaldo Garcia-Perez
Journal: Journal of Clinical Oncology (2023)

e16248 Background: PET/CT with somatostatin analogues (68 Ga DOTATOC) is essential for decision-making prior to treatment with [177Lu–Dota0–Tyr3]–Octreotate (177Lu-DOTATOC), there are biological characteristics in this type of neoplasms that allow predicting the response to therapy, the tumor burden is one of the most important variables, however its estimation with conventional imaging tools is limited, currently there are reconstruction algorithms based on artificial intelligence that allow estimating the tumor burden using molecular imaging studies with 68 Ga DOTATOC, aim of this work is to determine the value of the total tumor load with this radiotracer as a predictor of overall survival in patients treated with 177Lu DOTATOC. Methods: 45 patients (11 men and 34 women) with an average age of 57.2 (range 47.2 to 66.5) with histopathological and immunohistochemical diagnosis of well-differentiated neuroendocrine tumors (NETs) in the period from 2015 to 2021 who received therapy with (177Lu-DOTATOC) and who had a baseline 68Ga DOTATOC PET to calculate total tumor volume (TVV) and semiquantitative uptake values were retrospectively included. Results: The mean follow-up was 29.3 +/- 6 months. Using ROC curves, a cut-off point of 100 cm3 was determined to differentiate responding and non-responding patients. The difference in the overall survival curves between both groups was statistically significant (470 days vs. 180 days) with p=0.07. The main sites of origin of the primary tumor were pancreas (n=24), lung (n=11), small intestine (n=7) and liver (n=3). The mean tumor volume was 305.8 cm3 (+/- 272). The organs with the highest uptake values were pancreas with SUVmax of 27.9 (range 10.1-42.4), rectum with SUVmax 26.5 (10.7-42.3) and liver with SUVmax of 22.1 (14.4-31.7), these uptake values did not have any type of relation to patient survival. Regarding therapy with 177 Lu DOTATOC, 8 received 14.8 Gbq (400mCi), 12; 22.2 GBq (600mCi) and 25; 29.6 GBq (800 mCi), no serious adverse effect or kidney function impairment was demonstrated after 177Lu DOTATOC therapy. No grade 3 or 4 haematological toxicity was identified. Conclusions: PET/CT with 68 Ga-DOTATOC is routinely used in the management of patients with neuroendocrine tumors and also allows categorizing patients according to their tumor volume to predict overall survival in patients treated with 177 Lu-DOTATOC, thus in such a way that it could be considered as an easily accessible and widely available prognostic imaging biomarker.
Utility of artificial intelligence-based genomic classification of occult malignancies in clinical practice.
Authors: Sourat Darabi, Carlos E Zuazo, Taylor Brodie, Michael J. Demeure, David R. Braxton
Journal: Journal of Clinical Oncology (2023)

3065 Background: Occult primary malignancies (OPM) are a significant clinical problem, representing 3 to 5% of advanced cancers. Patients with OPM have a worse prognosis and fewer treatment options than when the primary site of origin of cancer can be confidently identified. Novel artificial intelligence-based genomic classification of occult malignancies has been validated for clinical use by previous studies, but reports of clinical utility have not yet been published. We report our experience of consecutive cases where a commercial AI-based genomic classifier was used in routine practice at a high-volume community cancer center. Methods: Malignancies with uncertain pathological classification or site of origin were subjected to molecular profiling and AI-based genomic classification (GPSai) capable of recognizing a set of 115 distinct primary tumor sites and histology classes. Molecular profiling consisted of whole exome and whole transcriptome sequencing of FFPE tumor samples along with other predictive biomarkers assays performed by a commercial laboratory (Caris Life Sciences). The identification of targetable mutations was reported, but variants of unknown significance were excluded when reporting genomic alterations. Results: From 1,316 patients between October 2021-November 2022, we analyzed 70 (5.3%) patients with OPM, including 44 (62.9%) females and 26 (37.1%) males, with 34 (48.6%) being 65 or older. GPSai classification was ordered for 73 samples from 70 patients, which resulted in the classification of 33 (45.2%) tumors, inconclusive results in 36 (49.3%), and insufficient tissue quantity in 4 (5.5%). Of the 33 cases with a GPSai classification, the putative pathology diagnosis was concordant in 26 (78.8%) and discordant in 7 (21.2%) cases. We investigated discordance between the GPSai and pathological diagnoses in discordant cases . The pathological classification was favored over GPSai in all 7 discordant cases. Of the 36 cases that could not be confidently assigned a classification, 14 (38.9%) possessed potentially actionable alterations . 23 of the 36 had no presumptive site of origin. Of these, 10 of 23 (43.5%) were PD-L1 positive, 4 of 23 (17.4%) had a high TMB, and 1 of 23 (4.4%) had MMR deficiency. Additionally, based on molecular profile and examination of RNA expression levels, 2 cases were able to be classified with subsequent IHC confirmation. Based on the results from genomic testing, 55.7% of patients (39 of 70) had FDA-approved treatment options. Conclusions: Over a third of patients with OPM were able to be assigned a cancer diagnosis concordant with diagnoses by pathologists. Of those which could not be classified, targetable biomarkers were commonly found. AI-based genomic classification of occult primaries is useful in clinical practice to help discern the site of origin and identify treatment options.
Assessment of patient reported outcomes (PROs) completion patterns in patients with cancer: Examining real-world data.
Authors: Nada Al-Antary, Eric Adjei Boakye, Samantha Tam, Carl Wilson, Laila Poisson, Theresa Zatirka, Michael Ryan, Kelly Hirko, Steven S. Chang, Benjamin Movsas
Journal: Journal of Clinical Oncology (2023)

6609 Background: Use of Patient Reported Outcomes (PROs) in clinical practice plays a major role in improving care, quality of life, hospitalization, emergency room visits and consequently improving overall survival. However, robust information on real-time assessment of PROs in cancer patients is insufficient, as most available data are limited to specific populations enrolled in clinical trials. This thereby increases disparities among minorities of race, age, and socioeconomic status, creating a barrier between the benefits of PROs and these underserved populations. This study examines the response rates, patterns and characteristics of patients completing PROs in a tertiary cancer center. Methods: Patients with a cancer diagnosis and an oncologic provider visit at a tertiary cancer center were offered an opportunity to complete Patient Reported Outcome Measures (PROMs) between August 2020 and July 2022.We used the National Institute of Health’s computer adaptive tests Patient-Reported Outcomes Measurement Information System (PROMIS) instruments in pain interference, physical function, fatigue, and depression. Seven days prior to their clinical appointment, patients were assigned the PROMIS instruments in MyChart, then offered in-clinic completion with a tablet at check-in, if not completed online. A decision tree model was employed to assess the factors that may influence patients' PROMs completion (age, gender, race, marital status, insurance, stage, comorbidity score, and provider specialty and location). Results: A total of 8,535 patients were offered the PROMIS CAT version 2.0 instrument during the study period. The two most important factors that determine whether a patient completed PROMs in order of importance were provider specialty and patient race. Patients were more likely to complete PROMs if they had a visit with a provider in Radiation Oncology (RC) or Surgery specialty compared with Medicine or Supportive Oncology specialty (40.86% versus 29.68%). Among patients who had a visit with a provider in RC or Surgery specialty, there was a better chance of PROMs completion with White race compared to Black or Other races (45.83% versus 33.69%). Of those who had a visit with a provider in Medicine or Supportive Oncology specialty, there was a better chance of PROMs completion with Other or White races compared to Black race (32.40% versus 22.19%). Conclusions: We found that provider specialty and patient race were the most important factors influencing patients’ PROMs completion. In order to realize the full benefit of PROs in patient care, multilevel interventions can be employed to increase patient-provider utilization of PROs. Moreover, efforts should focus on a patient-centered design to address patient and provider barriers impeding PROs accessibility and completion.
A phase I study of ruxolitinib in combination with abemaciclib for patients with primary or post-polycythemia vera/essential thrombocythemia myelofibrosis.
Authors: Jan Philipp Bewersdorf, Srdan Verstovsek, Andriy Derkach, Lucia Masarova, Naveen Pemmaraju, Eytan M. Stein, Michael J. Mauro, Raajit Rampal, Prithviraj Bose
Journal: Journal of Clinical Oncology (2023)

TPS7086 Background: Patients (pts) with myelofibrosis (MF) have a reduced life-expectancy compared to age-matched controls. Several oral Janus Kinase (JAK) inhibitors such as ruxolitinib (RUX) have been approved by the US FDA based on improvements in symptom burden and spleen volume reduction compared to physician’s choice of best available therapy. However, duration of response to these agents is generally time-limited and treatment with JAK inhibitors is not considered to have disease-modifying potential. Additionally, median overall survival after RUX discontinuation is only 11-14 months. Thus, novel mechanism-based therapies for pts with disease progression on RUX are needed. JAK2 V617F mutations promote transition from G1 to S-phase of the cell cycle via increased expression of CDC25A, which is also upregulated in primary MPN patient samples. Additional cell cycle regulators such as CDK6 and Cyclin D have also been implicated in MF pathogenesis. Finally, we and others have shown that combination of the CDK4/6 inhibitors and RUX had synergistic effects in murine models of MF (Rampal et al., CCR 2021) providing the preclinical rationale for this trial. Methods: This multicenter, phase I dose-escalation trial (NCT05714072) evaluates the safety of RUX + the CDK4/6 inhibitor abemaciclib in pts with primary or secondary MF with intermediate-1/2 or high-risk disease by DIPSS who require treatment and had an inadequate response to RUX. Among the currently FDA-approved CDK4/6 inhibitors, abemaciclib was chosen for combination therapy due to less myelosuppressive effects compared with other CDK4/6 inhibitors. Inadequate response to RUX is defined by (I) palpable splenomegaly ≥5 cm below the left costal margin at study entry AND/OR (II) active MPN symptoms, as defined by the presence of one symptom score ≥5 or two symptom scores ≥3 using the screening MPN-SAF TSS. Following a conventional “3+3” dose-escalation design, pts will be treated with increasing doses of abemaciclib and stable doses of RUX (10mg or 15mg BID). The primary endpoint is to determine the maximum tolerated dose of RUX + abemaciclib. Secondary endpoints include measures of efficacy. Exploratory endpoints include changes in allele fraction of driver mutations, gene expression profiling, and clonal architecture to identify biomarkers of response, mechanisms of resistance, and to assess for any disease-modifying effects of the combination therapy. This trial is open to enrollment at Memorial Sloan Kettering Cancer Center and MD Anderson Cancer Center. Clinical trial information: NCT05714072 .
A phase II trial with copanlisib plus avelumab as maintenance therapy for metastatic bladder cancer after platinum-based chemotherapy.
Authors: Hizra Farrukh, Zheng Zhu, Shaoming Zhu, Robert Bruce Montgomery, Joshua J Meeks, David James VanderWeele, Yu-Ning Wong, Robert A Lew, Chong-xian Pan
Journal: Journal of Clinical Oncology (2023)

TPS4610 Background: Bladder cancer is the tenth most common malignancy and the fourteenth most common cause of cancer death worldwide. Currently, platinum-based chemotherapy followed by avelumab maintenance immunotherapy is the first-line standard of care for advanced bladder cancer (aBC). Even though maintenance avelumab therapy has improved overall survival, its efficacy is still disappointing with a response rate of less than 10% and progression-free survival benefit of 1.7 months. The phosphoinositide 3-kinase (PI3K) pathway harbors more activating alterations than any other growth signaling pathway in aBC. Furthermore, PI3K δ and γ are expressed by immune cells and regulate their function. Activation alterations along the PI3K pathway are putative molecular drivers and can possibly be targeted for the treatment of aBC. In preclinical studies, we found that a pan-PI3K class I inhibitor, copanlisib, potentiates anti-programmed cell death 1 (PD1) antibody in syngeneic bladder cancer mouse models with or without activation alterations along the PI3K pathway (Zhu S, J Immunother Cancer. 2021). We hypothesize that copanlisib potentiates avelumab as maintenance therapy for aBC. Methods: This is a multi-center, single-arm, open-label Phase II trial with a lead-in safety phase to determine the efficacy and toxicity of combination copanlisib and avelumab maintenance therapy in aBC. The major inclusion criteria are patients with aBC without disease progression after platinum-based chemotherapy and no contraindication for avelumab and copanlisib. With a type I error of 5% and power of 80% with a log-rank test, we will need 26 patients for this study. With an attrition rate of 10%, we will enroll 29 patients from four US Department of Veterans Affairs Medical Centers. Copanlisib will be administered through intravenous infusion (IV) at 60 mg on Day 1, 8 and 15, and avelumab will be administered 800 mg IV on Day 1 and 15 of each 4-week treatment cycle for up to 26 cycles. Imaging will be repeated every two cycles during first year of therapy and thereafter every 3 cycles or clinically indicated. The primary endpoint is progression-free survival (PFS). The secondary endpoints include CT or MRI determined radiographic overall response rate, toxicity, overall survival, and molecular correlative studies. Kaplan-Meier estimates will be presented together with median PFS with 2-sided 95% confidence intervals (CI). In particular, the PFS rates at 3, 6, 9, 12 and 15 months will be estimated with corresponding 2-sided 95% CIs. Adverse events will be assessed according to CTCAE v5. Tumor response is determined according to Response Evaluation Criteria in Solid Tumors version (RECIST) 1.1 criteria. This study is currently open for enrollment. Clinical trial information: NCT05687721 .
Assessment of genomic profiling in patients with colorectal cancer treated in community oncology practices.
Authors: David Cosgrove, Emily Paul, Robyn Harrell, Janet L. Espirito, Nicholas J. Robert, Robert J. Oliver
Journal: Journal of Clinical Oncology (2023)

e15538 Background: Comprehensive genomic profiling is becoming the standard of care for oncology, though actionable biomarkers remain the focus. The value of expansion from single gene tests to large, next-generation sequencing (NGS) based tests can be seen in the application of precision medicine. Additionally, circulating tumor DNA (ctDNA) is becoming a key area of testing during and post treatment. In this study, we explored genetic testing rates in colorectal cancer (CRC) patients (pts). Methods: Pts were identified from the iKnowMed SM EMR data over 4 years (2018-2022) from 113 community oncology practices. Pts were required to have either primary colon or rectal cancer, be at least 20 yrs old at diagnosis, and have at least 2 office visits. All stages of disease were included. Genomic data was assessed from two sources: abstracted data from charts and genomics reports from clinical labs. Genomic tests included detection of mutations for relevant biomarkers, including but not limited to BRAF, KRAS, NRAS, NTRK, microsatellite instability (MSI), and tumor mutational burden (TMB), and entry of germline biomarkers relevant to Lynch syndrome. The use of ctDNA was also evaluated. Results: A cohort of 41,980 pts with CRC was identified. Median age was 66 yrs, 62% white. Of these, 18,782 pts (45%) had biomarker testing performed. Genomic testing rates were observed to have increased by 61% across all stages of disease over the four-year time span. The highest rate of biomarker testing was performed in pts with stage IV disease at diagnosis, representing 21% (n = 9021). Testing results were most often available for BRAF (n = 17576), with nearly 16% of the cohort showing a mutation, 35% of those with the V600E mutation (n = 967). MSI was observed in 14%. Increasing use of ctDNA observed, and 350 pts had multiple genetic reports (3+). Of the pts with genetic information, 245 were enrolled in clinical trials. Conclusions: In this study, we observed the increase of genetic profiling of CRC pts over time. Additional research into the use of targeted therapies and outcomes will be performed. The exploratory regions of the NGS-based assays tested may also provide new potential targets as the database of combined clinical and genetic information grows.
Sex difference in tolerability of adjuvant oxaliplatin-based chemotherapy for colorectal cancer and changes in diagnostic components of sarcopenia: A prospective study.
Authors: Hiroaki Nozawa, Shinya Abe, Kentaro Abe, Yumi Yokota, Mitsutaka Yakabe, Masahiro Akishita, Soichiro Ishihara
Journal: Journal of Clinical Oncology (2023)

e15625 Background: We previously reported that based on CT images at the 3rd lumbar vertebra, female patients with colorectal cancer (CRC) were more likely to be sarcopenic than male patients after curative resection, and predisposed to develop early dose limiting toxicities (DLTs) in adjuvant CAPOX therapy. Although oxaliplatin-based adjuvant chemotherapy for CRC is prevalently used worldwide, it is largely unknown how the treatment affects patients in terms of sarcopenia. Therefore we conducted a prospectively study on the impact of adjuvant chemotherapy on multifactorial components assessed for sarcopenia. Methods: We examined stage II-III CRC patients who received adjuvant CAPOX after curative surgery after March 2022. Informed consent was obtained from all participants. During this systemic therapy, we assessed nutritional status using Mini-Nutritional Assessment (MNA, an 18-item questionnaire consisting of psychological well-being, diet quality, physical activity and anthropometric metrics; score range:0-30), and examined gait speed and grip strength, as well as whole body skeletal muscle mass, fat mass, and bone mineral using a body composition analyzer. The changes in these metrics were analyzed in association with dose reduction/adverse events of CAPOX. All continuous variables were tested by Wilcoxon rank-sum test. Results: Eighteen men and 13 women (mean age: 61 years old) were included in this study. Seven (39%) male and seven (54%) female patients required dose reduction within the four treatment cycles (p = 0.65). The median MNA, gait speed, grip, muscle mass, fat mass and bone mineral at the first and fourth cycles of CAPOX in men were 20.4 and 24.0, 1.10 and 1.23 m/sec, 30.9 and 31.2 kg, 27.3 and 28.0 kg, 11.8 and 11.9 kg, and 2.8 and 2.9 kg, respectively. The median of these metrics at the first and fourth cycles of CAPOX in women were 21.4 and 22.4, 1.32 and 1.33 m/sec, 22.0 and 22.4 kg, 21.95 and 22.12 kg, 13.43 and 14.62 kg, and 2.34 and 2.31 kg, respectively. The relative values (medians) of the metrics at the fourth cycle to those at the first cycle of CAPOX (men vs women) were as follows; MNA:1.131 vs 1.045 (p = 0.057), gait speed:1.075 vs 0.950 (p = 0.17), grip:1.018 vs 1.044 (p = 0.81), muscle mass:1.028 vs 1.011 (p = 0.036), fat mass:1.029 vs 1.080 (p = 0.47), and bone mineral:1.030 vs 0.991 (p = 0.015). Conclusions: It is suggested that adjuvant CAPOX has negative impact on postoperative recovery of psychological and physical components in female patients.